5-13913776-A-G

Variant names:

• chr5-13913776-A-G
• rs3213936
• NM_001369.3:c.1503T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.1503T>C​(p.Ile501Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,612,792 control chromosomes in the GnomAD database, including 132,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15311 hom., cov: 32)
  • Exomes 𝑓: 0.39 (117302 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.487
• Publications: 22 publications found

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-13913776-A-G is Benign according to our data. Variant chr5-13913776-A-G is described in ClinVar as Benign. ClinVar VariationId is 163158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.487 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.1503T>C	p.Ile501Ile	synonymous	Exon 11 of 79	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.1503T>C	p.Ile501Ile	synonymous	Exon 11 of 79	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.1458T>C	p.Ile486Ile	synonymous	Exon 11 of 79	ENSP00000505288.1
	DNAH5	ENST00000508040.1	TSL:2	n.1911T>C		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66360 AN: 151726 Hom.: 15307 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.429

GnomAD2 exomes AF: 0.421 AC: 105718 AN: 251072 AF XY: 0.414

Gnomad AFR exome AF: 0.537

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.861

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.391 AC: 571673 AN: 1460948 Hom.: 117302 Cov.: 39 AF XY: 0.389 AC XY: 283053 AN XY: 726804

African (AFR) AF: 0.535 AC: 17880 AN: 33450

American (AMR) AF: 0.396 AC: 17689 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 11019 AN: 26118

East Asian (EAS) AF: 0.841 AC: 33344 AN: 39660

South Asian (SAS) AF: 0.358 AC: 30828 AN: 86222

European-Finnish (FIN) AF: 0.339 AC: 18089 AN: 53378

Middle Eastern (MID) AF: 0.434 AC: 2502 AN: 5766

European-Non Finnish (NFE) AF: 0.374 AC: 415530 AN: 1111278

Other (OTH) AF: 0.411 AC: 24792 AN: 60360

GnomAD4 genome AF: 0.437 AC: 66391 AN: 151844 Hom.: 15311 Cov.: 32 AF XY: 0.436 AC XY: 32333 AN XY: 74240

African (AFR) AF: 0.530 AC: 21958 AN: 41450

American (AMR) AF: 0.413 AC: 6296 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1422 AN: 3468

East Asian (EAS) AF: 0.852 AC: 4404 AN: 5170

South Asian (SAS) AF: 0.372 AC: 1795 AN: 4824

European-Finnish (FIN) AF: 0.327 AC: 3448 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25744 AN: 67824

Other (OTH) AF: 0.429 AC: 905 AN: 2110

Alfa AF: 0.395 Hom.: 17578

Bravo AF: 0.451

Asia WGS AF: 0.575 AC: 1997 AN: 3476

EpiCase AF: 0.384

EpiControl AF: 0.382

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia 3 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.83
DANN	Benign	0.64
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3213936; hg19: chr5-13913885; COSMIC: COSV54227062;